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Intrathecal Busulfan in Treating Patients With Recurrent, Refractory, or Metastatic Leptomeningeal Tumors

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
busulfan
Sponsored by
Duke University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring leptomeningeal metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed neoplasm that is metastatic in the cerebrospinal fluid or leptomeningeal/subarachnoid space Cytologic diagnosis of malignancy in the cerebrospinal fluid or neuroimaging evidence of leptomeningeal tumor by MRI Must have a recurrent or refractory leptomeningeal tumor Leptomeningeal tumors of leukemia, lymphoma, and all germ cell tumors must have also failed initial treatment or be recurrent No evidence of obstructive hydrocephalus or complete block of the spinal cerebrospinal fluid pathways on prestudy technetium Tc 99m albumin or indium In 111 DTPA flow study PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin less than 2.5 mg/dL SGOT or SGPT less than 1.5 times normal Renal: BUN less than 30 mg/dL Creatinine less than 1.5 mg/dL Calcium within normal limits Neurological: Neurological examination stable No rapidly progressing or deteriorating neurological deficits Other: No active infectious process Magnesium, phosphorus, potassium, chloride, and bicarbonate normal Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy Chemotherapy: At least 6 weeks since prior nitrosoureas or mitomycin At least 4 weeks since any other prior chemotherapy At least 3 weeks since prior intrathecal chemotherapy No other concurrent intrathecal chemotherapy Endocrine therapy: For patients on corticosteroids: Must be on a stable dose of corticosteroids for at least 1 week Radiotherapy: At least 3 weeks since prior radiotherapy to the CNS At least 4 weeks since any other prior radiotherapy No concurrent radiotherapy to the CNS Surgery: At least 3 weeks since prior surgery Other: No concurrent medication that may interfere with study results (e.g., immunosuppressive agents other than corticosteroids)

Sites / Locations

  • Duke Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
February 15, 2013
Sponsor
Duke University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003462
Brief Title
Intrathecal Busulfan in Treating Patients With Recurrent, Refractory, or Metastatic Leptomeningeal Tumors
Official Title
Phase I Study of Intrathecal Spartaject-Busulfan in Patients With Neoplastic Meningitis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
April 1998 (undefined)
Primary Completion Date
February 2001 (Actual)
Study Completion Date
February 2001 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs into the thin space between the lining of the spinal cord and brain may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of intrathecal busulfan in treating patients with recurrent, refractory, or metastatic leptomeningeal tumors.
Detailed Description
OBJECTIVES: Determine the maximum tolerated dose of intrathecal busulfan by a limited escalation dosage schedule in patients with recurrent or refractory leptomeningeal tumors. Determine the cerebrospinal fluid and serum pharmacokinetics of busulfan administered via intralumbar or intraventricular routes in these patients. OUTLINE: This is dose-escalation study. Patients receive intrathecal busulfan via intralumbar or intraventricular routes twice a week for 2 weeks (4 treatments). Any patient with objective or significant clinical response may continue treatment by receiving the same dose once a week for 2 consecutive weeks, once a week every other week for 3 weeks (2 treatments), and then once a month thereafter until disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of intrathecal busulfan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 12 weeks for 1 year or until disease progression. PROJECTED ACCRUAL: A total of 5-20 patients will be accrued for this study within 1-2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
leptomeningeal metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
busulfan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed neoplasm that is metastatic in the cerebrospinal fluid or leptomeningeal/subarachnoid space Cytologic diagnosis of malignancy in the cerebrospinal fluid or neuroimaging evidence of leptomeningeal tumor by MRI Must have a recurrent or refractory leptomeningeal tumor Leptomeningeal tumors of leukemia, lymphoma, and all germ cell tumors must have also failed initial treatment or be recurrent No evidence of obstructive hydrocephalus or complete block of the spinal cerebrospinal fluid pathways on prestudy technetium Tc 99m albumin or indium In 111 DTPA flow study PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin less than 2.5 mg/dL SGOT or SGPT less than 1.5 times normal Renal: BUN less than 30 mg/dL Creatinine less than 1.5 mg/dL Calcium within normal limits Neurological: Neurological examination stable No rapidly progressing or deteriorating neurological deficits Other: No active infectious process Magnesium, phosphorus, potassium, chloride, and bicarbonate normal Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy Chemotherapy: At least 6 weeks since prior nitrosoureas or mitomycin At least 4 weeks since any other prior chemotherapy At least 3 weeks since prior intrathecal chemotherapy No other concurrent intrathecal chemotherapy Endocrine therapy: For patients on corticosteroids: Must be on a stable dose of corticosteroids for at least 1 week Radiotherapy: At least 3 weeks since prior radiotherapy to the CNS At least 4 weeks since any other prior radiotherapy No concurrent radiotherapy to the CNS Surgery: At least 3 weeks since prior surgery Other: No concurrent medication that may interfere with study results (e.g., immunosuppressive agents other than corticosteroids)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henry S. Friedman, MD
Organizational Affiliation
Duke Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

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Intrathecal Busulfan in Treating Patients With Recurrent, Refractory, or Metastatic Leptomeningeal Tumors

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